Identification and characterisation of human xCT that co-expresses, with 4F2 heavy chain, the amino acid transport activity system xc-.

We have identified a new human complementary deoxyribonucleic acid (cDNA), for the xc- amino acid transporter (HGMW-approved name SLC7A11; also known as human xCT), that, when co-expressed with the heavy chain of surface antigen 4F2 (4F2hc, also termed CD98), but not with rBAT, (related to the bo,+ amino acid transporter), induces system xc- transport activity in Xenopus oocytes. Human xCT is the seventh human member of the family of amino acid transporters that are subunits of 4F2hc or rBAT and, inview of its amino acid sequence identity (89%) with mouse xCT, is most probably the human orthologue thereof. The amino acid transport activity induced by the co-expression of human 4F2hc and xCT in Xenopus oocytes was sodium independent and specific for L-cystine, L-glutamate and L-aspartate. This activity also functioned in an exchange mode (e.g. cystine/glutamate) with a substrate stoichiometry of 1:1. Expression of human xCT alone in oocytes did not induce amino acid transport activity and the expressed xCT protein was localised intracellularly. When human xCT was co-expressed with 4F2hc, the former localised to the oocyte plasma membrane. Tissue-expression studies showed that human SLC7A11 mRNA is expressed mainly in the brain, but also in pancreas and in cultured cell lines. The transport characteristics of human xCT and the distribution of its tissue expression strongly suggest that it corresponds to the human amino acid transporter system xc-.